Extracorporeal treatment of blood involves treatment of the whole blood or components thereof to remove or add a component or alter a blood component, and returning the treated blood to the mammal to obtain a desired effect. Sickle cell anemia can be treated by extracorporeal treatment of blood with ethacrynic acid, cyanate, or nitrogen mustard. Cholesterol levels can be lowered by extracorporeal treatment of blood with heparin-agarose beads to which low density plasma lipoproteins selectively bind. Beads of cross-linked agarose containing Fuller's earth or zirconium oxide powders have been used extracorporeally in blood detoxification to remove Paraquat or inorganic phosphates. Toxic effects of cisplatin used in treating human malignant glioma have been minimized by infusing cisplatin into the internal carotid artery and extracorporeally removing most of the cisplatin from the jugular venous flow by dialysis thereby minimizing the amount of cisplatin that enters the body below the neck. Other extracorporeal blood treatment methods include removal of T-cells, photopheresis where blood is exposed to ultraviolet light, removal of antibodies and immune complexes in the treatment of allergies, immune disorders, and systemic lupus erythematosus, and ion-exchange resin treatment of blood to improve serum protein binding of acidic drugs in patients having uremia.
The immunosuppressant macrolide FK-506 has been shown to be absorbed and retained by peripheral blood mononuclear cells and erythrocytes and to bind reversibly with a FK-506 binding protein (FKBP) in the erythrocytes. FK-506 inhibits the activation of T-lymphocytes and is available to the lymphocytes by dissociation from FKBP.
Daunomycin, an antileukemic drug, will not bind to red blood cells. If the red blood cells are first treated with Amphotericin B, a polyene macrolide that binds to sterols and perforates cell membranes, then the treated red blood cells will bind daunomycin. Mice bearing L1210 leukemic cells had a prolonged survival time when treated with erythrocytes with entrapped daunomycin. Other polyene macrolides, such as vacidin A and related compounds, bind with red blood cells and cause hemolysis to occur. The polyene macrolide antibiotic, faeriefungin, has erythrocyte toxicity similar to Amphotericin B.